Pharmacokinetic and toxicology studies of AYX2, a transcription factor decoy, non-opioid, disease modifying drug candidate for the long-term treatment of chronic pain

RESEARCH AND RELATED OTHER PROJECT INFORMATIONPROJECT SUMMARYABSTRACTFunding OpportunityPAPI NameMametJulienAs described by the HEAL Initiative Notice NOT NSthere currently exists an urgent unmet need for enhanced pain management in the form of safeeffectivenon opioid pain treatmentsChronic focal neuropathic painwhich includes pain etiologies such as radiculopathy and radiculitisfocal peripheral neuropathiesand low back painaffects as many asmillion patients annually in the United StatesThese conditions are commonly treated with opioid analgesicswith some patients subsequently experiencing addiction and abuseChronic focal neuropathic pain is maintained by genome wide transcription regulation in the dorsal root gangliaDRGspinal cord networkThe transcription factors driving this regulation constitute a promising class of targets with the potential to alter the course of pain with a single treatmentDNA decoys are oligonucleotides that specifically inhibit the activity of certain transcription factorsFollowing advancement of Adynxx s lead decoy programbrivoligideformerly AYXthe for treatment postoperative paininto Phaseclinical studiesAdynxx began development of its second decoy AYXfor altering the course of chronic painAYXbinds and inhibits Kr ppel like transcription factorsKLFandin the DRG spinal cordIn the Spared Nerve Injury and Chronic Constriction Injury rat models of chronic paina single intrathecalITinjection of AYXproduces a substantialweeks long reduction of pain compared to controlsThe goal of this Phaseproposal is to advance AYXtoward an IND submissionallowing for human clinical trialsWe propose in Aimto characterize AYXpharmacokinetics in the cerebrospinal fluid and plasma and its distribution in the DRGspinal cord and brain following an IT injectionWith this informationAYXwill be tested in a panel of complementary toxicology studies in Aimto allow for final IND enabling studiessupported by Phaseof the grantThis research will accelerate development of AYXas a novel drug candidate for the non opioid treatment of pain RESEARCH AND RELATED OTHER PROJECT INFORMATIONPROJECT NARRATIVEFunding OpportunityPAPI NameMametJulien Adynxx is currently developing a DNA decoy drug candidatebrivoligidewhich blocks the action of a transcription factor that is essential for the development of exacerbated pain after surgeryand which has reduced postoperative pain and opioid use in clinical trials conducted to date in a population of medically underserved patientsThis grant application seeks to support preclinical work needed to advance AYXa new DNA decoy drug candidate for the safe and long term treatment of chronic pain which blocks the action of transcription factors that are essential for the maintenance of chronic paininto clinical stage studiesPreclinical work performed to date indicates that a single intrathecal injection of AYXshould safely provide months of pain relief while minimizing the need for opioids in patientsin alignment with a recently announced interest of the HEAL initiative